The objective of the proposed grant is to assess the importance of complement in autoimmune and infectious diseases of the eye. Although little attention has been devoted to the role of complement in external diseases of the eye, preliminary work by the applicants indicates that complement fixation is associated with disease activity in ocular cicatricial pemphigoid and Mooren's ulcers and that properdin activation of the alternate pathway of complement is important in bacterial infections of the cornea. To determine the significance of complement in bacterial and fungal ulcerations of the cornea, we plan to decomplement rabbits prior to intracorneal injections of bacterial and fungal preparations. In addition, activators and components of the alternate pathway of complement will be injected intracorneally to determine if these agents alone are capable of inducing significant corneal infiltrations and ulcerations. Amino acid derivatives which inhibit the formation and lead to the disassociation of chemotactic complement complexes as well as other anti-inflammatory agents will be employed to modify the corneal response to injected materials. In this way, therapeutic approaches will be developed aimed at specific aspects of the host response. To assess the role of complement in external diseases of the eye, we must be able to detect complement even in low quantities. For this purpose, we plan to develop an improved and more sensitive method for direct immunofluorescent staining of complement in animal and human tissues. Furthermore, we plan to supplement this technique with ultrastructural studies of complement localization utilizing immunochemical methods. In this way, we will be able to determine more precisely the sites of complement binding and their relation to structural damage in tissues.